Document Detail

The role of the paraventricular nucleus of the hypothalamus in the regulation of cardiac and renal sympathetic nerve activity in conscious normal and heart failure sheep.
MedLine Citation:
PMID:  22615431     Owner:  NLM     Status:  MEDLINE    
The paraventricular nucleus of the hypothalamus (PVN) plays a major role in central cardiovascular and volume control, and has been implicated in controlling sympathetic nerve activity (SNA) during volume expansion and in heart failure (HF). The objectives were to determine the role of the PVN on cardiac and renal SNA (CSNA and RSNA) in conscious normal sheep and sheep with pacing-induced heart failure. In normovolaemic sheep in the normal state and in HF, bilateral microinjection of the GABA agonist muscimol (2 mm, 500 nl), had no effects on resting mean arterial pressure (MAP), heart rate (HR), CSNA or RSNA. In addition, neither chemical inhibition of the PVN using the inhibitory amino acid glycine (0.5 m, 500 nl), nor electrolytic lesion of the PVN reduced the elevated level of CSNA in HF. Dysinhibition of the PVN with bilateral microinjection of bicuculline (1 mm, 500 nl) in normal sheep increased MAP, HR and CSNA, but decreased RSNA, whereas in HF bicuculline had no effects on MAP, HR or CSNA, but inhibited RSNA. During volume expansion in normal sheep, muscimol reversed the inhibition of RSNA, but not of CSNA. In summary, removal of endogenous GABAergic inhibition to the PVN indicated that CSNA is normally under inhibitory control. Although this inhibition was absent in HF, the responses to pharmacological inhibition, or lesion of the PVN, indicates that it does not drive the increased CSNA in HF. These findings indicate the PVN has a greater influence on RSNA than CSNA in the resting state in normal and HF sheep, and during volume expansion in normal sheep.
Rohit Ramchandra; Sally G Hood; Robert Frithiof; Michael J McKinley; Clive N May
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-21
Journal Detail:
Title:  The Journal of physiology     Volume:  591     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-13     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  93-107     Citation Subset:  IM    
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MeSH Terms
Bicuculline / pharmacology
GABA-A Receptor Agonists / pharmacology
GABA-A Receptor Antagonists / pharmacology
Glycine / pharmacology
Glycine Agents / pharmacology
Heart / physiology*
Heart Failure / physiopathology*
Kidney / physiology*
Muscimol / pharmacology
Neurons / physiology
Paraventricular Hypothalamic Nucleus / physiology*
Sympathetic Nervous System
Reg. No./Substance:
0/GABA-A Receptor Agonists; 0/GABA-A Receptor Antagonists; 0/Glycine Agents; 2763-96-4/Muscimol; TE7660XO1C/Glycine; Y37615DVKC/Bicuculline
Comment In:
J Physiol. 2013 Jan 1;591(Pt 1):1   [PMID:  23281481 ]

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